The present invention relates to a series of novel 6-(4-substituted phenyl)-1,2,4-triazin-3(2H)-one derivatives and provides processes for their preparation, methods of using them and compositions containing them. The compounds of the invention are characterized by having a 1,2,4-triazin-3(2H)-one group at the 1-position of the phenyl ring and a substituent on the 4-position of the phenyl group, which substituent is chosen from a limited class of substituted carbonylalkoxy or carbonylalkylthio groups.
The compounds of the invention have exhibited a variety of valuable therapeutic activities, including a cardiotonic activity (notably a stimulant activity arising from potentiation of the contractions of the heart), anti-hypertensive activity, the ability to inhibit gastric secretions and the ability to inhibit blood platelet aggregation; however, it is envisaged that the primary value of the compounds of the invention will arise as a result of their cardiotonic activity.
A variety of 6-(substituted phenyl)-3(2H)-1,2,4-triazinones is known, and some of these are thought to have useful cardiac activities. For example, certain such compounds are said in European Patent Publication No. 52 442 to have cardiotonic and vasodilator activities. Other, somewhat similar, compounds are disclosed in European Patent Publication No. 123 254 and are said to have anti-hypertensive activity, the ability to inhibit gastric secretions and the ability to inhibit blood platelet aggregation, whilst those disclosed in European Patent Publication No. 122 627 are said to be useful in the treatment of hypertension, thrombosis and ulcers in human beings and other animals. British patent specification No. 1 383 906 (equivalent to U.S. patent specifications No. 3 975 388 and No. 4 088 762) and Japanese Patent Application Kokai (i.e. as laid open to public inspection) No. 8015/83 also disclose compounds which are said to have anti-hypertensive activity, but these are pyridazinone derivatives, unlike the 1,2,4-triazin-3(2H)-one derivatives of the present invention.
The compounds of European Patent Publication No. 123 254 are triazinone derivatives and the compounds of European Patent Publication No. 52 442 include some triazinone derivatives. However, the triazinone derivatives of this prior art differ from the compounds of the present invention in that the compounds of the invention all contain certain specified substituted carbonylalkoxy or carbonylalkylthio substituents on the 4-position of the phenyl group, and we have surprisingly found that compounds containing such a substituent possess significantly better cardiotonic activity than do the prior art compounds.